Purpose: Introduction: Sustained release of protein in the polymer implants has presented a formulation challenge because of protein stability issue, especially at elevated temperatures. In this study, bovine serum albumin (BSA) was selected as a model protein, to assess the stabilization effect of HPβCD and PVP on protein solid formulation at elevated temperatures. In this study, the effect of HPβCD, PVP on BSA stability in a spray-dried formulation at temperatures ranging from 80 to 150 °C was investigated. BSA is a structurally well characterized protein which contains 583 amino acid. It was reported that formulated injectable BSA solution forms disulfide-linked BSA aggregates and gelation. Thermal treatment also alters the secondary and tertiary structures, denatures the protein and causes aggregation.
When solid protein dosage form is desirable, lyophilization (freeze drying) is one of the most common processing method for the formulation of biopharmaceuticals with the increased stability and shelf life. Lyophilization requires days to remove the moisture with significant time and energy cost. Spray drying converts a liquid formulation quickly into a dry powder in minutes by atomizing the solution into fine droplets followed by the quick drying in a large chamber using heated gas. Comparing with lyophilization, spray drying is time and cost efficient. Objective of the study is to understand the stabilization effect of HPβCD and PVP on protein formulation during spray drying using BSA as a model protein with trehalose used as protectant control.
Purpose: To investigate the stabilization effect of HPβCD, and PVP in BSA SDD formulation during spray drying.
Methods: Size exclusion HPLC (SEC) is used to monitor the aggregation of BSA. Stock solution was prepared by weighing 10.0 g of BSA, 1.550 g of Histidine into 1L volumetric flask followed by the addition 600 mL of phosphate buffer solution (1XPBS), gently vortex until dissolve, then q.s to 1000 mL.
Results: HPβCD (CavitronTM W7) and PVP (C-12) are better than trehalose in the SDD process at temperatures ranging from 80 to 150 °C with less aggregation after spray drying. SDD formulations using HPβCD, PVP, and trehalose stored at normal, and accelerated storage conditions for 2 weeks (Figure 3) are comparable or better in term of the monomer purity.
Conclusion: HPβCD/PVP provide better protection on BSA than trehalose during the spray drying process. Then demonstrate similar stabilization effect with trehalose at normal and accelerated storage condition during storage for 2 weeks.
Wucheng Wen– Ashland Specialty Ingredients, Delaware
Kamaru Lawal– Ashland Specialty Ingredients
Yunxia Bi– Technical Director, Ashland Specialty Ingredients
Thomas Dürig– Senior Director, Ashland Specialty Ingredients, Wilmington, Delaware